This application is for renewal of the Nathan Shock Center of Excellence in the Basic Biology of Aging at the University of Washington and affiliated institutions. This Center has over the past 15 years provided resources in support of our large community of investigators that are funded to study basic biological mechanisms of aging. We continue to build upon a scientific theme that became established in the past funding cycle, in which comparative gerontologic study informed us of conserved genetic pathways of longevity determination (the TOR pathway is an example of one such). The three proposed Research Resources Core components are well suited to assist in such efforts: 1) Transgenic Animal Model Development; 2) Functional Assessment; 3) Functional Genomics. The Transgenic Animal Model Development Resource Core continues to pursue a focus on inducible gene expression and knockout models, so that organ and age-specific effects of genetic alterations can be assessed. The Functional Assessment Core builds upon technical resources that have been gathered during the past funding period, such that we can now provide investigators with a broad and informative range of physiologic and cellular assays, including those that are most relevant to assessment of the healthspan of mouse models. The Functional Genomics Core provides expert assistance with state of the art technologies for transcriptomics and proteomics. Consistent with our theme, it includes a focus on translational state, protein turnover and post-translational modification. The Research Development Core will continue to support pilot study projects in the basic biology of aging. The Program Enrichment Core supports administrative management, an external advisory panel, a program of courses and seminars and data sharing and dissemination.